- Jose
C. Masdeu, M.D., Ph.D., Pamplona, Spain
- masdeu@unav.es
Neuroimaging facilitates the diagnosis and
treatment of several nervous system disorders,
including:
This overview highlights recent or more
critical developments in the application of imaging to the
treatment of each of these disorders.
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Stroke
Computed tomography (CT) is still the
modality of choice in most places for the imaging
of acute stroke. CT defines the presence of hemorrhage and
allows for the use of thrombolysis when
-
there is no hemorrhage
-
if present, the area of hipodensity
is no larger than one/third of the middle cerebral artery
territory
-
less than three hours have elapsed
since onset
-
and other
conditions are met
In many instances, the lack of time, or
of additional imaging techniques will not allow for a more
precise course of action. Ideally, thrombolysis should be
avoided when
-
the damage is so small that no
benefit will result
-
the vascular endothelium has been
damaged in a relatively large area, predisposing the patient
to a hemorrhage if thrombolysis is used. As a tissue
resistant to hypoxia, the endothelium is only damaged by
profound ischemia.
There are imaging techniques
that facilitate the identification of these two
conditions:
- Perfusion
CT, measuring perfusion time can provide an estimate
of the viability of the various ischemic brain
regions.
- Brain single photon computed
tomography (SPECT) depicts the area and
degree of ischemia. Normal studies, or studies showing
large areas of severe ischemia would contraindicate
thrombolysis.
- Even more accurate data on
brain perfusion can be gained with
H215O positron emission tomography
(PET), but this technique is less widely available.
- Perfusion
magnetic resonance imaging (MRI) depicts the area of
decreased flow, whereas diffusion
MRI depicts areas of ischemia. Areas of decreased
perfusion not still ischemic (perfusion-diffusion
mismatch) are good targets for thrombolysis.
- MR
angiography allows for determination of arterial
recanalization with thrombolysis.
The identification of the cause of
ischemia or hemorrhage in a stroke is an important step to
treatment. For instance, an aneurysm should be obliterated by
endovascular means or clipped. A patient with cardiac
embologenic disease may need cardiac surgery or chronic
anticoagulation. To visualize the blood vessels and the heart
four techniques are mostly used:
A goal for the rapid treatment of stroke
is to be able to image the brain and the heart in 30 minutes.
A goal not still attainable, but the subject of current
research and technological developments.
Stroke Prevention
Neuroimaging is critical for several
therapeutic procedures leading to stroke prevention. Such
are:
-
Angioplasty and stenting
of stenotic extracranial or endocranial arteries
- Obliteration of
- berry aneurysms
- arteriovenous malformations
-
Stenting of arteries with
traumatic aneurysms
Epilepsy
In addition to the diagnosis of epileptogenic
lesions, such as brain tumors, neuroimaging is now used for
the identification of abnormal epileptogenic brain tissue,
which can be surgically removed, often with excellent
results.
MRI is the first-line study. This
technique allows for the identification of:
When MRI fails to help localize
adequately the origin of the seizures, two other imaging
techniques are available:
Dementia
Progressive cognitive decline is often produced
by Alzheimer's disease (AD). CT or MRI can be used to rule out
rare
tumors or
other lesions that can cause a somewhat similar clinical
picture, as indicated in the 2001
Guidelines of the American Academy of Neurology.
Other differential diagnostic
considerations that may be clarified with neuroimaging
include:
The arrival of donepezil and other
anticolinesterase medications, and of memantine, makes it
relevant to diagnose these conditions more accurately, as some
of them respond more readily to the medications.
As even more active therapies are being
developed, trying to prevent the excessive deposit of beta
amyloid, or even facilitating its removal from the brain, it
is becoming clearer that an early diagnosis is important, if
possible at the preclinical stages.
Several techniques have been used to
predict which patients with mild cognitive impairment are more
likely to develop progressive cognitive decline:
Removal of amyloid by vaccines or
antibodies has been effective in transgenic mice and has been
tried in a preliminary clinical trial, halted when several
patients developed encephalitis, likely on an immune-mediated
basis.
Visualization with PET of the
deposition of
amyloid in the brain of patients with Alzheimer was
reported in the summer of 2002.
Tumors
In clinical gene-therapy trials for recurrent
glioblastomas, transduction of the herpes simplex virus type-1
thymidine kinase (HSV-1-tk) gene with subsequent prodrug
activation by ganciclovir was found to be safe, but clinical
response was poor.
PET has been used to depict the
extent of HSV-1-tk gene expression, which seemed to
predict the therapeutic response.
Neuroimaging is critical for the
performance of
stereotactic radiosurgery,
to remove small tumors and obliterate small arteriovenous
malformations.
Functional neuroimaging allows for the
identification of
cortical regions critical for movement and speech. Tumors
near these areas can be more safely resected when such
information is available to the neurosurgeon.
Multiple Sclerosis
Treatment of patients with the first
episode may be justified,
according to the new McDonald
criteria, if dissemination in time and space can be
concluded from MRI studies in a given patient.
The effectiveness of new therapies for
multiple sclerosis, including interferon
beta and antibody-mediated
suppression of T cell subtypes, is being evaluated by
serial MRI, an excellent tool to detect subclinical disease
progression.
The
"open ring" sign distinguishes
giant multiple sclerosis plaques from tumors or infections,
with which can be easily mistaken on CT or MRI.
Infections
The treatment of brain abscesses may be
facilitated by the feasibility of same-day
outpatient biopsy, which also saves resources.
Increased signal on FLAIR and
diffusion-weighted MRI helps in the diagnosis of
Creutzfeldt-Jakob
disease. In this disorder, signal is increased in:
-
Striatum
-
Pulvinar
-
Dorsomedial thalamus
Movement and Gait
Disorders
Electrical modulation of the
subthalamic nuclei, with implanted electrodes, improves
Parkinson's disease. Electrode placement is facilitated by
accurate neuroimaging procedures, using MRI or CT.
Pallidal stimulation is effective for the treatment of
dystonia and stimulation of the ventrolateral nucleus of the
thalamus helps patients with severe essential tremor
Gait disorders can be caused by
treatable disorders, such as hydrocephalus, or subdural
hematomas, amenable to diagnosis by CT or MRI.
Anxiety
The combination of genetics and functional
neuroimaging is being used as a powerful tool to clarify many
brain pathologies, as a means to finding more powerful
therapies that could then be tailored to the individual
(pharmaco-genomics).
As an example, functional
MRI has illustrated greater neuronal activity in response
to fearful stimuli in the amygdala of individuals with the
short allele of the serotonin transporter (5-HTT) promoter
polymorphism, which has been associated with reduced 5-HTT
function and increased fear and anxiety-related
behaviors.
Additional Reading
Phelps
ME. Inaugural article: positron emission tomography
provides molecular imaging of biological processes.
Proc
Natl Acad Sci U S A. 2000 Aug 1;97(16):9226-33.
Lawler
A. Drug-abuse research. White House stirs interest in
brain-imaging initiative. Science. 2002 Aug
2;297(5582):748-9.
Kirshner
HS. Behavioral neurology in the emergency room: language
testing, brain imaging, and acute stroke therapy.
Ann
Neurol. 2001 Nov;50(5):559-60.
Lok
C. Picture perfect.
Nature. 2001 Jul
26;412(6845):372-4
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